The NIH-sponsored Training Program in Investigative Rheumatology, begun at Yale in 1976, has the philosophy that a portion of biomedical scientists, both M.D.'s and Ph.D.'s, should be trained in an environment that focuses upon mechanisms of rheumatologic and immunologic diseases. This belief is grounded in the notion that the challenges involved in understanding these illnesses requires a cohort of investigators whose knowledge and training enable them to span the gaps between basic biology and clinical rheumatology and immunology. Hence, our goals are to attract individuals to our program who are interested in learning about fundamental mechanisms of disease and the applications of this knowledge. Our program is focused upon bench research, with an emphasis on providing fundamental training in immunology, microbiology, and cellular and molecular biology; is comprised of both physician and Ph.D. trainees; and has for its training faculty a highly collaborative group of 16 physician-scientists (M.D. and M.D./Ph.D.) and basic scientists in the Sections of Rheumatology and Allergy and Clinical Immunology in the Department of Medicine, in the Section of Immunobiology, and in the Department of Biology. The quality, cohesiveness, and diverse skills of these mentors, along with the innate skills and the desire of our trainees, are the most important requisites for success of our program. Four trainees (M.D. and Ph.D.) per year are currently supported by the NIH-Sponsored Training Program in Investigative Rheumatology, and four positions per year are requested in this competitive renewal. M.D. trainees typically perform clinical work in the first year of their fellowship (supported by clinical funds), and then enter the lab at the beginning of their second year. We prepare these individuals for the likely possibility of spending at least three, and sometimes four or five, full years in the lab (making our total program at least four years for M.D. fellows, in contrast to the typical three years for the Ph.D. fellows). The combination of both M.D. and Ph.D. fellows serves two purposes: it gives the M.D. fellows a much better lab experience, and it exposes the Ph.D. fellows to opportunities to apply their skills to rheumatologic problems, with the goal of cementing their aspirations, expressed upon selection for our training program, for long term careers in investigations of rheumatic and immunologic diseases. Fellows supported by this Training Grant work side-by-side with a diverse group of trainees (undergraduate, medical and Ph.D. students, and M.D. and Ph.D. postdoctoral fellows) that currently numbers over 130, and they receive didactic as well as interactive instruction in basic biology, laboratory techniques, and ethical issues in science. As designed, this program provides our trainees with the foundation in basic science that will enable them to bridge the differences between basic research and fundamental approaches to understanding rheumatologic and immunologic illnesses.